Genetic characterization of human KB cell lines resistant to epidermal growth factor: Pseudomonas exotoxin conjugates

Pleiotropic human KB cell mutants, selected for resistance to a conjugate of epidermal growth factor with Pseudomonas exotoxin (PE-EGF), were characterized genetically. These mutants have a pleiotropic phenotype, which includes reduced number of EGF receptors and reduced growth rate. Hybrid cells between HeLa D98 and four out of five of these resistant cell lines were more resistant to PE-EGF than hybrids formed between HeLa D98 and parental KB cells. This result indicates that the phenotype of PE-EGF resistance is incompletely dominant in four out of five cases and recessive in one out of five variants. In three separate experiments, transfection of DNA from two of the dominant resistant cell lines resulted in transformation of wild-type KB cells to PE-EGF resistance, confirming the dominant nature of these mutations, which affect levels of EGF receptor in KB cells.